The Experts below are selected from a list of 1585236 Experts worldwide ranked by ideXlab platform
Eric O Long - One of the best experts on this subject based on the ideXlab platform.
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t cell Response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:Abstract In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DRα paired with the β chain encoded by DRB5*0101) and DR2b (DRα paired with the β chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131–159) are uniquely restricted by DR2a. The immunodominant middle epitope (81–99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell Response. Overall, immunodominance in the MBP-specific T cell Response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell Response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
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t cell Response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell Response. Overall, immunodominance in the MBP-specific T cell Response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell Response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
Jia Liu - One of the best experts on this subject based on the ideXlab platform.
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impaired cytotoxic cd8 t cell Response in elderly covid 19 patients
Mbio, 2020Co-Authors: Jaana Westmeier, Krystallenia Paniskaki, Zehra Karakose, Tanja Werner, Kathrin Sutter, Sebastian Dolff, Marvin Overbeck, Andreas Limmer, Jia LiuAbstract:ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell Response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell Response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic Response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell Responses in COVID-19 patients that may also have important implications for vaccine development. IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell Response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic Response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.
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impaired cytotoxic cd8 t cell Response in elderly covid 19 patients
bioRxiv, 2020Co-Authors: Jaana Westmeier, Krystallenia Paniskaki, Zehra Karakose, Tanja Werner, Kathrin Sutter, Sebastian Dolff, Marvin Overbeck, Andreas Limmer, Jia Liu, Xin ZhengAbstract:Abstract SARS-CoV-2 infection induces a T cell Response that most likely contributes to virus control in COVID-19 patients, but may also induce immunopathology. Until now, the cytotoxic T cell Response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic Response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B, as well as perforin within different effector CD8+ T cell subsets. PD-1 expressing CD8+ T cells also produced cytotoxic molecules during acute infection indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provides valuable information about T cell Responses in COVID-19 patients that may also have important implications for vaccine development. Importance Cytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell Response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic Response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients.
Kathrin Sutter - One of the best experts on this subject based on the ideXlab platform.
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impaired cytotoxic cd8 t cell Response in elderly covid 19 patients
Mbio, 2020Co-Authors: Jaana Westmeier, Krystallenia Paniskaki, Zehra Karakose, Tanja Werner, Kathrin Sutter, Sebastian Dolff, Marvin Overbeck, Andreas Limmer, Jia LiuAbstract:ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell Response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell Response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic Response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell Responses in COVID-19 patients that may also have important implications for vaccine development. IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell Response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic Response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.
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impaired cytotoxic cd8 t cell Response in elderly covid 19 patients
bioRxiv, 2020Co-Authors: Jaana Westmeier, Krystallenia Paniskaki, Zehra Karakose, Tanja Werner, Kathrin Sutter, Sebastian Dolff, Marvin Overbeck, Andreas Limmer, Jia Liu, Xin ZhengAbstract:Abstract SARS-CoV-2 infection induces a T cell Response that most likely contributes to virus control in COVID-19 patients, but may also induce immunopathology. Until now, the cytotoxic T cell Response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic Response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B, as well as perforin within different effector CD8+ T cell subsets. PD-1 expressing CD8+ T cells also produced cytotoxic molecules during acute infection indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provides valuable information about T cell Responses in COVID-19 patients that may also have important implications for vaccine development. Importance Cytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell Response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic Response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients.
Andreas Stefferl - One of the best experts on this subject based on the ideXlab platform.
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Butyrophilin, a Milk Protein, Modulates the Encephalitogenic T Cell Response to Myelin Oligodendrocyte Glycoprotein in
2013Co-Authors: Experimental Autoimmune Encephalomyelitis, Andreas Stefferl, Anna Schubart, Aminullah Amini, Hans Lassmann, Maria Storch, Ian Mather, Christopher LiningtonAbstract:Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune disease that reproduces the inflammatory demyelinating pathology of multiple sclerosis. We report that an encephalitogenic T cell Response to MOG can be either induced or alternatively suppressed as a consequence of immunological cross-reactivity, or “molecular mimicry ” with the extracellular IgV-like domain of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory Response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages. We demonstrate that this pathology is mediated by a MHC class II-restricted T cell Response that cross-reacts with the MOG peptide sequence 76–87, IGEGKVALRIQN (identities underlined). Conversely, molecular mimicry with BTN can be exploited to suppress disease activity in MOG-induced EAE. We demonstrate that not only is EAE mediated by the adoptive transfer of MOG74–90 T cell lines markedly ameliorated by i.v. treatment with the homologous BTN peptide, BTN74–90, but that this protective effect is also seen in actively induced disease following transmucosal (intranasal) administration of the peptide. These results identify a mechanism by which the consumption of milk products may modulate the pathogenic autoimmune Response to MOG. The Journal of Immunology
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butyrophilin a milk protein modulates the encephalitogenic t cell Response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis
Journal of Immunology, 2000Co-Authors: Andreas Stefferl, Anna Schubart, Maria K Storch, Aminullah Amini, Ian H Mather, Hans Lassmann, Christopher LiningtonAbstract:Experimental autoimmune encephalomyelitis (EAE) induced by sensitization with myelin oligodendrocyte glycoprotein (MOG) is a T cell-dependent autoimmune disease that reproduces the inflammatory demyelinating pathology of multiple sclerosis. We report that an encephalitogenic T cell Response to MOG can be either induced or alternatively suppressed as a consequence of immunological cross-reactivity, or "molecular mimicry" with the extracellular IgV-like domain of the milk protein butyrophilin (BTN). In the Dark Agouti rat, active immunization with native BTN triggers an inflammatory Response in the CNS characterized by the formation of scattered meningeal and perivascular infiltrates of T cells and macrophages. We demonstrate that this pathology is mediated by a MHC class II-restricted T cell Response that cross-reacts with the MOG peptide sequence 76-87, I GEG KVA LRIQ N (identities underlined). Conversely, molecular mimicry with BTN can be exploited to suppress disease activity in MOG-induced EAE. We demonstrate that not only is EAE mediated by the adoptive transfer of MOG74-90 T cell lines markedly ameliorated by i.v. treatment with the homologous BTN peptide, BTN74-90, but that this protective effect is also seen in actively induced disease following transmucosal (intranasal) administration of the peptide. These results identify a mechanism by which the consumption of milk products may modulate the pathogenic autoimmune Response to MOG.
Rafi Ahmed - One of the best experts on this subject based on the ideXlab platform.
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initial viral load determines the magnitude of the human cd8 t cell Response to yellow fever vaccination
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Rama Akondy, Philip L F Johnson, Helder I Nakaya, Srilatha Edupuganti, Mark J Mulligan, Benton Lawson, Joseph D Miller, Bali Pulendran, Rustom Antia, Rafi AhmedAbstract:CD8 T cells are a potent tool for eliminating intracellular pathogens and tumor cells. Thus, eliciting robust CD8 T-Cell immunity is the basis for many vaccines under development. However, the relationship between antigen load and the magnitude of the CD8 T-Cell Response is not well-described in a human immune Response. Here we address this issue by quantifying viral load and the CD8 T-Cell Response in a cohort of 80 individuals immunized with the live attenuated yellow fever vaccine (YFV-17D) by sampling peripheral blood at days 0, 1, 2, 3, 5, 7, 9, 11, 14, 30, and 90. When the virus load was below a threshold (peak virus load < 225 genomes per mL, or integrated virus load < 400 genome days per mL), the magnitude of the CD8 T-Cell Response correlated strongly with the virus load (R(2) ∼ 0.63). As the virus load increased above this threshold, the magnitude of the CD8 T-Cell Responses saturated. Recent advances in CD8 T-Cell-based vaccines have focused on replication-incompetent or single-cycle vectors. However, these approaches deliver relatively limited amounts of antigen after immunization. Our results highlight the requirement that T-Cell-based vaccines should deliver sufficient antigen during the initial period of the immune Response to elicit a large number of CD8 T cells that may be needed for protection.
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quantitating the magnitude of the lymphocytic choriomeningitis virus specific cd8 t cell Response it is even bigger than we thought
Journal of Virology, 2007Co-Authors: David Masopust, Kaja Muralikrishna, Rafi AhmedAbstract:Measuring the magnitudes and specificities of antiviral CD8 T-Cell Responses is critical for understanding the dynamics and regulation of adaptive immunity. Despite many excellent studies, the accurate measurement of the total CD8 T-Cell Response directed against a particular infection has been hampered by an incomplete knowledge of all CD8 T-Cell epitopes and also by potential contributions of bystander expansion among CD8 T cells of irrelevant specificities. Here, we use several techniques to provide a more complete accounting of the CD8 T-Cell Response generated upon infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV). Eight days following infection, we found that 85 to 95% of CD8 T cells exhibit an effector phenotype as indicated by granzyme B, 1B11, CD62L, CD11a, and CD127 expression. We demonstrate that CD8 T-Cell expansion is due to cells that divide >7 times, whereas heterologous viral infections only elicited <3 divisions among bystander memory CD8 T cells. Furthermore, we found that approximately 80% of CD8 T cells in spleen were specific for ten different LCMV-derived epitopes at the peak of primary infection. These data suggest that following a single LCMV infection, effector CD8 T cells divide ≥15 times and account for at least 80%, and possibly as much as 95%, of the CD8 T-Cell pool. Moreover, the Response targeted a very broad array of peptide major histocompatibility complexes (MHCs), even though we examined epitopes derived from only two of the four proteins encoded by the LCMV genome and C57BL/6 mice only have two MHC class I alleles. These data illustrate the potential enormity, specificity, and breadth of CD8 T-Cell Responses to viral infection and demonstrate that bystander activation does not contribute to CD8 T-Cell expansion.
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chimeric yellow fever dengue virus as a candidate dengue vaccine quantitation of the dengue virus specific cd8 t cell Response
Journal of Virology, 2000Co-Authors: Robbert G Van Der Most, Rafi Ahmed, Kaja Muralikrishna, James H StraussAbstract:We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-Cell Response specific for the DEN-2 virus prM and E proteins. This Response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune Responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-Cell Response.
